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Biomedical subjects

V Brown

Publications and source records attributed to V Brown.

At least 19 recordsLinked to original sources
PubMed1999

Elevated levels of a U4/U6.U5 snRNP-associated protein, Spp381p, rescue a mutant defective in spliceosome maturation.

U4 snRNA release from the spliceosome occurs through an essential but ill-defined Prp38p-dependent step. Here we report the results of a dosage suppressor screen to identify genes that contribute to PRP38 function. Elevated expression of a previously uncharacterized gene, SPP381, efficiently suppresses the growth and splicing defects of a temperature-sensitive (Ts) mutant prp38-1. This suppression is specific in that enhanced SPP381 expression does not alter the abundance of intronless RNA transcripts or suppress the Ts phenotypes of other prp mutants. Since SPP381 does not suppress a prp38::LEU2 null allele, it is clear that Spp381p assists Prp38p in splicing but does not substitute for it. Yeast SPP381 disruptants are severely growth impaired and accumulate unspliced pre-mRNA. Immune precipitation studies show that, like Prp38p, Spp381p is present in the U4/U6.U5 tri-snRNP particle. Two-hybrid analyses support the view that the carboxyl half of Spp381p directly interacts with the Prp38p protein. A putative PEST proteolysis domain within Spp381p is dispensable for the Spp381p-Prp38p interaction and for prp38-1 suppression but contributes to Spp381p function in splicing. Curiously, in vitro, Spp381p may not be needed for the chemistry of pre-mRNA splicing. Based on the in vivo and in vitro results presented here, we propose that two small acidic proteins without obvious RNA binding domains, Spp381p and Prp38p, act in concert to promote U4/U5.U6 tri-snRNP function in the spliceosome cycle.

Amino Acid Sequence↗
PubMed1998

Using the eye-movement system to control the head.

We tested the hypothesis that A.I., a subject who has total ophthalmoplegia, resulting in a lack of eye movements, used her head to orientate in a qualitatively similar way to eye-based orientating of control subjects. We used four classic eye-movement paradigms and measured A.I.'s head movements while she performed the tasks. These paradigms were (i) the gap paradigm, (ii) the remote-distractor effect, (iii) the anti-saccade paradigm, and (iv) tests of saccadic suppression. In all cases, A.I.'s head saccades were qualitatively similar to previously reported eye-movement data. We conclude that A.I.'s head movements are probably controlled by the same neural mechanisms that control eye movements in unimpaired subjects.

Adult↗
PubMed1998

Purified recombinant Fmrp exhibits selective RNA binding as an intrinsic property of the fragile X mental retardation protein.

Fragile X syndrome is caused by the transcriptional silencing of the FMR1 gene due to a trinucleotide repeat expansion. The encoded protein, Fmrp, has been found to be a nucleocytoplasmic RNA-binding protein containing both KH domains and RGG boxes that associates with polyribosomes as a ribonucleoprotein particle. RNA binding has previously been demonstrated with in vitro-translated Fmrp; however, it remained uncertain whether the selective RNA binding observed was an intrinsic property of Fmrp or required an associated protein(s). Here, baculovirus-expressed and affinity-purified FLAG-tagged murine Fmrp was shown to bind directly to both ribonucleotide homopolymers and human brain mRNA. FLAG-Fmrp exhibited selectivity for binding poly(G) > poly(U) >> poly(C) or poly(A). Moreover, purified FLAG-Fmrp bound to only a subset of brain mRNA, including the 3' untranslated regions of myelin basic protein message and its own message. Recombinant isoform 4, lacking the RGG boxes but maintaining both KH domains, was also purified and was found to only weakly interact with RNA. FLAG-purified I304N Fmrp, harboring the mutation of severe fragile X syndrome, demonstrated RNA binding, in contrast to previous suggestions. These data demonstrate the intrinsic property of Fmrp to selectively bind RNA and show FLAG-Fmrp as a suitable reagent for structural characterization and identification of cognate RNA ligands.

Animals↗
PubMed1998

Thermolabile methylenetetrahydrofolate reductase polymorphism (C677T) and total homocysteine concentration among African-American and white women.

A polymorphism associated with a thermolabile variant (C677T) of the enzyme methylenetetrahydrofolate reductase has been associated with both elevated total homocysteine (tHcy) levels and risk for cardiovascular disease. Data from the Stroke Prevention in Young Women Study were used to determine the prevalence of the C677T genotype and to assess whether environmental factors modified the association between genotype and tHcy concentration. The C677T genotype prevalence was 80% -/-, 20% +/-, and 0% +/+ among 46 African-American women; and 39% -/-, 53% +/-, and 8% +/+ among 77 white women (P < 0.01). There was a trend toward higher tHcy levels in African-American women with the +/- genotype when compared with the -/- genotype (6.9 mumol/L vs 5.3 mumol/L respectively, p = 0.10); no association was found among the white women (6.0 mumol/L, -/-; 4.5 mumol/L, +/-; and 6.2 mumol/L, +/+; p = 0.67). Among African American women, those who smoked and were +/- genotype had the highest tHcy levels (8.0 mumol/L); while among white women, those who smoked and were -/- had the highest tHcy levels (8.1 mumol/L). Despite being hampered by a limited sample size, the thermolabile allele is significantly less common among African-American than white women. The association between genotype and tHcy concentration is influenced by smoking and multivitamin use.

Adolescent↗
PubMed1997

FMRP associates with polyribosomes as an mRNP, and the I304N mutation of severe fragile X syndrome abolishes this association.

Fragile X mental retardation is caused by the lack of FMRP, a selective RNA-binding protein associated with ribosomes. A missense mutation, I304N, has been found to result in an unusually severe phenotype. We show here that normal FMRP associates with elongating polyribosomes via large mRNP particles. Despite normal expression and cytoplasmic mRNA association, the I304N FMRP is incorporated into abnormal mRNP particles that are not associated with polyribosomes. These data indicate that association of FMRP with polyribosomes must be functionally important and imply that the mechanism of the severe phenotype in the I304N patient lies in the sequestration of bound mRNAs in nontranslatable mRNP particles. In the absence of FMRP, these same mRNAs may be partially translated via alternative mRNPs, although perhaps abnormally localized or regulated, resulting in typical fragile X syndrome.

Animals↗
PubMed1997

Face detection in peripheral vision: do faces pop out?

We examined whether faces can produce a 'pop-out' effect in visual search tasks. In the first experiment, subjects' eye movements and search latencies were measured while they viewed a display containing a target face amidst distractors. Targets were upright or inverted faces presented with seven others of the opposite polarity as an 'around-the-clock' display. Face images were either photographic or 'feature only', with the outline removed. Naive subjects were poor at locating an upright face from an array of inverted faces, but performance improved with practice. In the second experiment, we investigated systematically how training improved performance. Prior to testing, subjects were practised on locating either upright or inverted faces. All subjects benefited from training. Subjects practised on upright faces were faster and more accurate at locating upright target faces than inverted. Subjects practised on inverted faces showed no difference between upright and inverted targets. In the third experiment, faces with 'jumbled' features were used as distractors, and this resulted in the same pattern of findings. We conclude that there is no direct rapid 'pop-out' effect for faces. However, the findings demonstrate that, in peripheral vision, upright faces show a processing advantage over inverted faces.

Adult↗
PubMed1997

Effects of amount of attention allocated to the location of visual stimulus pairs on perception of simultaneity.

This study was examined whether a change in the amount of attention equally allocated to two locations affects judgments of the simultaneity or successiveness of stimuli presented at those locations. Observers were cued to expect two brief flashes either to the left and right of fixation or above and below fixation. Stimulus onset asynchrony was randomly varied. On a small proportion of trials, the stimuli appeared at the unexpected locations. Observers were more likely to report the stimuli as simultaneous when they appeared in the unexpected locations. A model proposed to account for the data assumes that a brief stimulus event is represented by a probability distribution reflecting the uncertainty in determining the time of the event's occurrence, and two events are judged to be simultaneous if they are perceived to fall within some critical temporal interval, c, which is a function of the amount of attention allocated to the task.

Adult↗
PubMed1997

The child in theatre: should parents be involved?

In this article the author will discuss the parental role in relation to children undergoing surgery. The gap between theory and practice in relation to this issue is recognised, and an inter-relationship which must occur has been described (McCaugherty 1991). The principles of theory are valuable, but it is only through application to practice that problems can be properly identified. Equally, the ability to deal with such problems as they arise can only occur when the underpinning knowledge of theory enables foresight. The author will examine theories and research into parental involvement in their child's care whilst the child is in the operating department and discuss problems which have arisen during application to practice.

Adult↗
PubMed1997

[Competency of newly qualified nurses following completion of the 4-year diploma program].

The purpose of this study was to determine the competency of newly qualified nurses practitioners in a curative setting after completion of the 4 Year Diploma Course at Otto du Plessis Nursing College. The respondents evaluated their skills and abilities by completing a questionnaire which was developed by the research committee after consultation with the services. The need to assess competency comes from the desire to have a relevant curriculum enabling the newly qualified nurse to practice in a variety of health settings at all levels of care. The degree of competency related to practice in a curative setting was selected for particular attention because most newly qualified nurses in the target group were still employed in a curative milieu. Findings revealed various deficits or inadequacies in competency levels and recommendations were made to adapt the curriculum.

Clinical Competence↗